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Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing., Author Summary How neurons generate output spikes in response to various combinations of inputs is a central issue in contemporary neuroscience. Due to their large dendritic tree and complex intrinsic properties, cerebellar Purkinje cells are an important model system to study this input-output transformation. Here we examine how noise can change the parameters of this transformation. In experiments we found that spike generation in Purkinje cells can be efficiently inhibited by noise of a particular amplitude. This effect is called inverse stochastic resonance (ISR) and has previously been described only in theoretical models of neurons. We explain the mechanism underlying ISR using a simple model matching the properties of experimentally characterized Purkinje cells. We found that ISR is present in Purkinje cells when the mean input current is near threshold for spike generation. ISR can be explained by the co-existence of resting and spiking solutions of the simple model. Changes of the input noise variance change the lifetime of these resting and spiking states, suggesting a mechanism for a tunable filter with long time constants implemented by a Purkinje cell population in the cerebellum. Finally, ISR leads to locally optimal information transfer from the input to the output of a Purkinje cell.